Endothelium and cannabinoid receptor involvement in levcromakalim vasorelaxation.
Levcromakalim was more potent at relaxing rat small mesenteric arteries with endothelium (EC50, 84+/-10 nM) than denuded vessels (EC50, 779+/-101 nM). The cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride; 1 microM) shifted the levcromakalim concentration/response curve 7.6-fold rightwards in intact vessels but had no effect in de-endothelialised vessels. Similar effects occurred with pinacidil. Combination of the K+ channel blockers apamin (1 microM) and charybdotoxin (100 nM) shifted the levcromakalim concentration/response curve 3-fold rightwards only in intact vessels. It is concluded that levcromakalim and pinacidil relax mesenteric arteries partly by releasing a relaxing factor from endothelium, possibly an endogenous cannabinoid.
White
R
R
Department of Pharmacology, University of Cambridge, UK.
Hiley
C R
CR
D000818:Animals; D019806:Cromakalim / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D020110:Pinacidil; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D000077285:Rimonabant; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D010880:Piperidines; D015221:Potassium Channels; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil; D000077285:Rimonabant